Community-acquired pneumonia: levofloxacin increased clinical success.

Clinical bottom line (level 1b)

  1. Patients with community-acquired pneumonia who were given levofloxacin were more likely to have clinical success than those given ceftriaxone or cefuroxime (NNT = 17 at 7 days) .
  2. Patients who were given levofloxacin had no clear difference in relapse than those given ceftriaxone or cefuroxime.
  3. There was no clear difference in adverse effects.
File et al: Antimicrobial Agents and Chemotherapy 1997; 41: 1965-1972
Expires March 2003

The study

Unblinded ?concealed randomised trial with intention-to-treat
Setting: 40 centres, USA

590 patients (aged range 18 to 93 years; mean 50, 55% male) primary diagnosis of community-acquired pneumonia- new pulmonary infiltrate (on chest roentagraph), compatible with opneumonia and two or more signs and symptoms consistent with lower respiratory tract infection (elevated temperature, new or increased cough, production of purulent sputum, rales or pleuritic chest pain and shortnss of breath.

Excluded if
  • infections due to organisms known to be resistant to study drug prior to entry
  • cystic fibrosis or fungal infection
  • empyema
  • HIV and CD4 counts of <200 cells/mm ³
  • neutropenia (<500 cells/mm ³ )
  • hospital-acquired infections
  • requiring a second systemic antimicrobial agent
  • history of seizures or a major psychiatric disorder
  • history of allergy to a study drug or to ß -lactam or quinolone antimicrobial agents
  • pregnacy or nursing
  • severe renal impairment (creatinine clearance of <20 ml/min)
  • received an investigational agent within 30 days of study entry
  • previous antimicrobial therapy for >24 hours


    • Note:
  • 66% of patients were caucasian.
  • The investigator could switch between ceftriaxone and cefuroxime axetil at any time if such a change was clinically indicated.
  • Patients receiving ceftriaxone or cefuroxime could also be given oral or iv erythromycin at a dosage of 500 mg to 1 g every 6 hours if atypical respiratory pathogens were suspected or proven (doxycycline could be given instead if the patient could not tolerate erythromycin).
  • Reasons for not clinically evaluating some patients were insufficient therapy, inappropriate timing of posttherapy clinical evaluation, no posttherapy evaluation, other protocol violations, unconfirmed clinical diagnosis, effective concomitant therapy and unevaluable for safety.


    • Control Group: (n = 295, 230 analysed): ceftraxone intravenously at a dosage of 1 or 2g once or twice daily for 7 to 14 days or cefuroxime axetil (orally) at 500 mg twice daily for 7 to 14 days
    Experimental Group: (n = 295, 226 analysed): levofloxacin intravenously as a 1 hour infusion ata dosage of 500 mg once daily or orally at 500 mg once daily for 7 to 14 days

    99% followed for 28 days
    Outcome notes:
    • clinical success : cure (resolution of signs and symptoms associated with active infection along with improvement in chest roengenogram findings) or improvement (incomplete resolution of signs, symptoms and chest roentgenogram findings)

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    clinical success 7 days 207
    (90.0%)    		 217
    (96.0%)    		 60%
    (16% to 81%)    		 6.02%
    (1.38% to 10.66%)    		 17
    (9 to 73)
    posttherapy relapse 28 days 4
    (1.74%)    		 6
    (2.65%)    		 -53.0%
    (-434% to 56.0%)    		 -0.92%
    (-3.61% to 1.78%)    		 -109
    (NNT = 56 to infinity;
    NNH = 28 to infinity)
    drug-related adverse effects 28 days 25
    (8.47%)    		 17
    (5.76%)    		 32.0%
    (-23.0% to 62.0%)    		 2.71%
    (-1.43% to 6.86%)    		 37
    (NNT = 15 to infinity;
    NNH = 70 to infinity)

    Comments

    1. Restricted use of fluoloquinolones has been suggested to avoid the spread of resistant organisms

    Citation

    1. File TM, Segreti J, Dunbar L, et al: Multicenter, randomized study comparing efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with commiunity-acquired pneumonia. Antimicrobial Agents and Chemotherapy 1997; 41: 1965-1972
    Search Terms: community-acquired pneumonia and therapy in Medline
    Contributor: Clare Wotton and Musab Hayatli, November 1999
    Reviewer: Mitsuhiro Kamei

    Clinical Question.
    Patient community-acquired pneumonia
    Intervention or Exposure levofloxacin
    Comparison ceftriaxone and/or cefuroxime
    Outcome clinical success